The invention relates to reagents for cross-linking pressure-sensitive adhesive formulations on the basis of silicone polymers.
Apart from other technical applications, such pressure-sensitive adhesive formulations are mainly employed in the manufacture of medicinal patches. Among the medicinal patches, these silicone pressure-sensitive adhesives which are cross-linked in a novel manner are especially suited for the production of active substance-containing medicinal patches, i.e. of transdermal therapeutic systems (TTS).
The described cross-linking reagents are employed according to the invention in the solvent containing coating and drying of pressure-sensitive silicone adhesive formulations.
It is only under these conditions that the reagents develop their cross-linked action, which results in the formation of a three-dimensional polymer network.
The resultant pressure-sensitive adhesive layers thereby lose their flowabilityxe2x80x94their so-called xe2x80x9ccold flowxe2x80x9d.
Cold flow is an undesirable phenomenon because when it occurs, two surfaces bonded to each other by a pressure-sensitive adhesive layer can be displaced relative to each other even under the influence of gravity, so that a position-constant bond between these surfaces cannot be ensured.
In the case of TTS, this problem especially concerns the adhesive bonding of the system to the application site on humans or animals. Furthermore, when cold flow sets in within the silicone adhesive layer comprised in the TTS, the influence of gravity and of cohesion and adhesion forces can result in undesirable deformation and shifting within the system even during storage.
It has now surprisingly been found that the cross-linked reagents employed in the cross-linked of polyacrylate-based pressure-sensitive adhesives can also be successfully used with silicone polymers, despite the fact that the chemical properties of said silicone polymers are fundamentally different from those of polyacrylates.
organometallic complexes of certain metal cations have proved to be especially effective. Among these, complexes of metals such as aluminum, titanium, zirconium or zinc are particularly preferred according to the invention. As an organic complex former, acetylacetone is particularly suited for medical application.
The cross-linked reagents are added to the solution of the silicone pressure-sensitive adhesive and develop their cross-linked action only after the solvents or stabilizing additives have been removed by drying.
Pressure-sensitive adhesives based on silicone polymers are of particular significance in medical application. This is due to their excellent dermatological compatibility with regard to the triggering of skin irritations and immunological reactions (sensibilization, allergization). In addition, silicone pressure-sensitive adhesives are products which adhere to human skin reliably and over a longer period of time, up to several days. Their strongly water-repellent nature also plays a role in this context.
In the TTS field, silicone pressure-sensitive adhesives stand out for their good chemical compatibility with pharmaceutical active agents and auxiliary substances, which promotes the chemical stability and storability of products based on said adhesives. The unusually high permeability (diffusibility) of the silicone polymers, which facilitates the release of contained active and auxiliary agents, is also of particular significance.
Besides these advantages, the silicone pressure-sensitive adhesives available on the market for medicinal application (e.g. product line Bio-PSA Q7 by Dow Corning Company) show considerable deficits as regards their rheological properties.
These products are polysiloxane-based polymers exhibiting no three-dimensional cross-linked or only one limited to microscopic areas. They have a structure that is substantially threadlike and branched to only a small extent or not at all.
This is necessary so that the products can be dissolved at all in organic solvents such as e.g. short-chain alkanes (heptane, petrol) or ethyl acetate, and so that they can be subjected to solvent containing processing.
Furthermore, these prior art polymers are one-component polymer solutions.
One-component means that the polymers contained in the solution are not intended, in their further processing; for a two-component reaction in the known sense of resin and hardener.
One-component does not however, mean that the solution may not contain more than one type polysiloxane polymer, optionally also in admixture with chemically different polymers (e.g. polyacrylates). The procedures employed in the processing of one-component polysiloxane pressure-sensitive solutions described in the following must not be confused with those procedures and catalysts that have been described in manifold ways for two-component silicone adhesives. Such systems contain at least two different types of polysiloxane which are intended, during their further processing, for a reaction yielding a three-dimensional polymer network in the sense of resin and hardener.
The term polysiloxane also comprises mixed polymers of polysiloxane to whose polymer chains chemically different sections, for example on the basis of polyethylene oxide, polypropylene oxide, polyvinyl pyrrolidone or poly(meth)acrylate, are incorporated or added.
In the field of TTS production, the processing of polysiloxane pressure-sensitive adhesive solutions comprises spreading and drying to form thin, pressure-sensitive polymer films.
In the processed state, the lack of three-dimensional cross-linked proves a disadvantage, as the threadlike polymer chains retain a certain flowability, even if an extremely slow one. This is referred to as xe2x80x9ccold flowxe2x80x9d by the experts since it occurs even at room temperature.
The following forces can all promote such a flow:
1. gravity
2. all mechanical forces that may have an effect on the product during production or storage,
3. adhesion forces between the pressure-sensitive polymers and the surfaces they cover (resulting in contraction or spreading)
4. cohesion forces in the polymer itself (contraction).
Cold flow practically always has disadvantageous effects during the storage of TTS, which may typically be for a period of two years or more. In this way, e.g. conglutination of the products with their packages may result.
The phenomenon also undesirably arises upon application to the human or animal skin, especially promoted by the warm body temperature. When the TTS is worn for several hours or days, the result may be a displacement thereof caused by the TTS practically flowing over the skin. Furthermore, the silicone pressure-sensitive adhesive may spread on the skin by slowly flowing beyond the area originally provided with adhesive This frequently leads to residue remaining on the skin along the marginal area of the system after removal of the system. This residue is regarded as extremely annoying by the user.
The problem of cold flow in silicone pressure-sensitive adhesives is known. U.S. Pat. No. 5,232,702 describes a large number of possible countermeasures. The document mentions various types of fillers and additives; however, none of these is described as a cross-linked reagent.
In connection with activesubstance systems, cross-linked reactions are even expressly described as being problematic or impossible because the required temperatures are too high or because of a lacking biocompatibility of the reagents (column 5, lines 3-10).
A great number of other cohesion-enhancing measures are described instead.
As these measures do not, in practice, always enable the control of the problem, it was the object of the invention to provide novel and more efficient methods for suppressing cold flow in silicone pressure-sensitive adhesives.
This object is surprisingly achieved by adding reagents which are employed for the suppression of cold flow in a chemically completely different family of pressure-sensitive adhesive polymers, namely polyacrylates.
This transferred applicability was not to be expected since polysiloxane, as the skeletal structure of silicone polymers, are of a completely different chemical nature than polyacrylates, which are built up of pure hydrocarbon chemistry.